GSBS Student Publications

Title

Isoform-specific regulation of Akt signaling by the endosomal protein WDFY2.

Student Author(s)

Xiarong Shi; Deanna M. Navaroli

Publication Date

2010-05-07

UMMS Affiliation

Graduate School of Biomedical Sciences, Interdisciplinary Graduate Program; Program in Molecular Medicine

Document Type

Article

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Recent work has led to the identification of novel endocytic compartments with functional roles in both protein trafficking and growth factor signal transduction. The phosphatidylinositol 3-phosphate binding, FYVE domain-containing protein WDFY2 is localized to a distinct subset of early endosomes, which are localized close to the plasma membrane. Here, we find that the serine/threonine kinase Akt interacts with these endosomes in an isoform-specific manner. Using quantitative fluorescence microscopy we demonstrate specific co-localization of WDFY2 with endogenous Akt2, but not Akt1. Moreover, depletion of WDFY2 leads to impaired phosphorylation of Akt in response to insulin due to isoform specific reduction of Akt2, but not Akt1, protein levels, and to a marked reduction in the insulin-stimulated phosphorylation of numerous Akt substrates. This is accompanied by an impairment in insulin-stimulated glucose transport and, after prolonged silencing, a reduction in the level of expression of adipogenic genes. We propose that WDFY2-enriched endosomes serve as a scaffold that enables specificity of insulin signaling through Akt2.

Source

J Biol Chem. 2010 May 7;285(19):14101-8. Epub 2010 Feb 26.

Journal/Book/Conference Title

The Journal of biological chemistry

Related Resources

Link to article in PubMed

PubMed ID

20189988

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